Na-dependent cationic drug (ethidium, acriflavine, 2-N-methyl ellipticinium, berberine, norfloxacin, ciprofloxacin, rhodamine 6G, crystal violet, doxorubicin, novobiocin, enoxacin, and tetraphenylphosphonium chloride) efflux pump, NorM (Long et al. 2008). 3-d structures of the N. gonorrheae NorM transporter (96% identical to the N. miningitidis protein) have been solved complexed with three different substrates in a multidrug cavity and Cs (4HUN; Lu et al. 2013). Lu et al. an identified an uncommon cation-π interaction in the Na+-binding site located
outside the drug-binding cavity and validated the biological relevance
of both the substrate- and cation-binding sites by conducting drug
resistance and transport assays. Additionally, they observed a potential
rearrangement of at least two transmembrane helices upon Na+-induced
drug export. They suggested
that Na+ triggers multidrug extrusion by inducing protein
conformational changes rather than by directly competing for the
substrate-binding amino acids. However, see 2.A.66.1.32 where the opposite was concluded for a homologue that functions by drug:H+ antiport.

Human MATE1 electroneutral organocation:H antiporter (transports tetraethylammonium, TEA and cimetidine as well as cisplatin and oxaliplatin) (Yonezawa et al., 2006). MATE1 also exports chloroquine across the luminal membrane (Müller et al., 2011). It has an established 13 TMS topology with the "extra" TMS in an extracellular C-terminal region that is not essential for function (Zhang et al., 2012). Also exports 1-methyl-4-phenylpyridinium (MPP), N-methylnicotinamide
(NMN), metformin, creatinine, guanidine, procainamide, topotecan,
estrone sulfate, acyclovir, ganciclovir and the zwitterionic
cephalosporin, cephalexin and cephradin. Seems to also play a role in
the uptake of oxaliplatin (a platinum anticancer agent). Able to
transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used
herbicid. Responsible for the secretion of cationic drugs across the
brush border membranes (Tanihara et al. 2007).

Multidrug:proton antiporter of the DinF subfamily. The structure has been solved to 3.2 Å resolution with and without the substrate, Rhodamine 6 G. The 12 TMSs show asymmetry with a membrane-embedded substrate-binding chamber. Direct competition between the H+ and the substrate during transport was suggested (Lu et al. 2013). However, the opposite was suggested for a sodium antiporter (see TC# 2.A.66.1.10).

Multidrug exporter, DinF, of 457 aas. Exports various toxic compounds, including antibiotics, phytoalexins, and detergents. Mutants are less virulent on the tomato plant than the wild-type strain (Brown et al. 2007).

Multidrug resistance protein, CdeA of 441 aas. Exports ethidium bromide, fluoroquinolone and acriflavin but had no effect on susceptibility to the following antibiotics: norfloxacin, ciprofloxacin,
gentamicin, erythromycin, tetracyclin, and chloramphenicol (Dridi et al. 2004). May be a Na+ antiporter.

Homologue of Mte1 of Tricholomp vaccinum of 588 aas which mediates detoxification of xenobiotics and metal ions
such as Cu, Li, Al, and Ni, as well as secondary plant metabolites (Schlunk et al. 2015).

Transparent Testa 12 (TT12), also called Protein DETOXIFICATION, is a valuolar transporter of proanthocyanidins (PAs). It transports these compounds from the cytoplasm into the vacuolar lumen (Gao et al. 2015).

MATE family transporter of 475 aas and 12 TMSs in a 6 + 6 TMS pseudosymmetic arrangement. The 3-d structure has been determined at 2.9 Å resolution (Tanaka et al. 2017). The protein possesses a negatively charged internal pocket with an outward-facing shape. This structure was determined for the C. sativa orthologue of the C. rubella protein, the sequence of which is 94% identical to the one provided here.

Detoxification protein, DTX35, of 614 aas and 12 TMSs, also called FLOWER FLAVONOID TRANSPORTER (FFT), encodes a MATE
family transporter in Arabidopsis thaliana. FFT (AtDTX35) is highly
transcribed in floral tissues, the transcript being localized to
epidermal guard cells, including those of the anthers, stigma, siliques
and nectaries (Thompson et al. 2010). The absence of FFT affects flavonoid levels in the plant. Moreover, root growth, seed
development and germination, and pollen development, release and
viability are all affected (Thompson et al. 2010). Also functions as a chloride channel, which, together with DTX33, is essential for turgor regulation (Zhang et al. 2017). Involved in floral development (Song et al. 2017).

MATE2 or Detoxification 47 (DTX47) of 543 aas and 12 TMSs. The orthologs from several plants have been sequenced and characterized (i.e., wheat; potato) (Li et al. 2018). This protein may be a citrate and salicylate exporter and promote resistance to aluminum (Al3+) (Garcia-Oliveira et al. 2018).

MATE drug:sodium symporter of 461 aas and 12 TMSs. The crystal structure is known (3VVO, 3VVP, 3VVR, 3VVS) in two distinct apo-form conformations, and in complexes with a
derivative of the antibacterial drug norfloxacin and three in vitro
selected thioether-macrocyclic peptides, at 2.1-3.0 Å resolutions. The structures, combined with functional analyses, show that the
protonation of Asp 41 on the amino (N)-terminal lobe induces the bending
of TMS1, which in turn collapses the N-lobe cavity, thereby extruding
the substrate drug to the extracellular space. Moreover, the macrocyclic
peptides bind the central cleft in distinct manners, which correlate
with their inhibitory activities (Tanaka et al. 2013). The Na+-binding site, in the N-lobe of this transporter, is selective against K+, weakly specific against H+, and broadly conserved among prokaryotic MATEs (Ficici et al. 2018).

The mouse virulence factor, MviN. (May flip the Lipid II peptidoglycan precursor from the cytoplasmic side of the inner membrane to the periplasmic surface) (Vasudevan et al., 2009). MviN, a putative lipid flippase (Fay and Dworkin, 2009). In E. coli, MviN is an essential protein which when defective results in the accumulation of polyprenyl diphosphate-N-acetylmuramic acid-(pentapeptide)-N-acetyl-glucosamine. This may be the peptidoglycan intermediated exported via MviN (Inoue et al. 2008). It is essential for the growth of several bacteria.

Peptidoglycan biosynthesis protein MurJ (Ruiz 2008). A 3-d structural model showed a solvent-exposed cavity within the
plane of the membrane (Butler et al. 2013). MurJ has 14 TMSs, and specific charged residues localized in the central cavity are essential for
function. This structural homology model suggests that MurJ functions as an essential transporter in PG biosynthesis (Butler et al. 2013). Based on an in vivo assay, MurJ is a flippase for the lipid-linked cell wall precursor, polyisoprenoid-linked disaccharide-peptapeptide (Sham et al. 2014). There is controversy about the role of this porter and FtsW/RodA which on the basis of an in vitro assay, were thought to be flippases for the same intermediate (Young 2014).

MurJ (MviV) of 475 aas and 14 TMSs. Kuk et al. 2016 presented a
crystal structure of MurJ from Thermosipho africanus in an inward-facing conformation at 2.0-A
resolution. A hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into
a large central cavity that is mostly cationic. Their results suggest that alternating access is important for MurJ function, which may
be applicable to other MOP superfamily transporters (Kuk et al. 2016).

Wzx isoprenoid-linked O-antigen precursor glycan translocase. A 12 TMS topology with N- and C-termini in the cytoplasm has been estabilshed, and functionally important residues have been identified (Marolda et al. 2010). A substrate:proton antiport mechanism has been established (Islam et al. 2013).